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TESTING OUTCOMES FOR A NEW ASEPTIC ABDOMINAL DRESSING TO PROTECT AND HYDRATE EVENTRATED ORGANS USING EXPERIMENTAL MODEL OF THE OPEN ABDOMINAL TRAUMA
Golovko K.P., Adamenko V.N., Boyarintsev V.V., Trofimenko A.V., Toropova Ya.G., Denisov A.V., Suborova T.N., Zhirnova N.A., Zaychikov D.A., Kudarov M.A., Dmitrieva E.V., Sidelnikova O.P.
Kirov Military
Medical Academy,
Almazov National
Medical Research Centre, Saint Petersburg, Russia,
Moscow Physico-Technical Institute (National Research
University), Moscow, Russia
Currently, abdominal injuries consist for 1.9-8 %
among combat injuries. The proportion of severe injuries reaches 70.8 % [1, 2]. N.I. Pirogov wrote about gun-shot abdominal injuries:
“None of cavities is so variable and difficult to diagnose as abdominal one”
[3]. One should note that abdominal injuries were the most common cause of
lethal outcomes in military medical facilities [4].
Eventration of abdominal organs is the absolute signs
of the penetrating abdominal injury, with 35 % of patients with eventration
among penetrating injuries [5]. The incidence of eventration of hollow
abdominal organs was 10.8 % in the Afghanistan and North Caucasus war conflicts
[6]. The true eventration is complicated by abdominal cavity contamination in
100 % of cases. It causes such severe complications as intestinal obstruction
and postsurgical peritonitis [7]. If a surgery lasts for 20 minutes and more,
interintestinal adhesions appear [8]. Infectious complications in 54.1 % and peritonitis
(43.3 %) cause the lethal outcome in penetrating abdominal injuries [4, 6].
The retrospective analysis of 583 cases in the data
base (Afghanistan, North Caucasus) of the military field surgery department of Kirov
Military Medical Academy showed 5.8 % of abdominal injuries with eventration of
hollow organs (34/583). Among them, complications appeared in 73.5 % of cases
(25/34). Peritonitis was the main complication (44.1 %, 15/25). Lethal outcomes were in 50 % (17/34).
In compliance with the modern guidelines of Defense
Ministry of RF (2013), eventrated organs are not inserted, but are covered with
aseptic dressing when performing the first aid for patients with abdominal
injury and eventration [7]. At the stage of medical care it is recommended to
use the improvised dressings: eventrated organs are covered with sterile
dressings with liquid paraffin; along the perimeter, they are protected from
compression with gauze doughnut-shaped dressing and are fixed with the circular
dressing (with cotton wool for warming in cold time) [6, 10]. Some authors recommend
to moisture the dressing with 0.9 % sodium chloride during transportation [5].
The equipment of Russian military forces includes the individual dressing
wrapper (IDW) and it modifications in view of cotton gauze pads with roll gauze.
In civilian healthcare, according to the protocol for urgent medical care [11],
the recommended care corresponds to the volume of first medical care.
According to the instructions to prehospital medical
care arrangement, the plastic dressing package, which preserves the organs from
water losses, is used in the armies of North Atlantic Treaty. Its sterile side
is placed onto eventrated organs. Then the dressing is applied, and standard or
improvised gauze [12]. In Israeli security services, army and police, the
compression abdominal dressing is used. This special bandage is the hybrid of
gauze, IDW, tourniquet and dense compressing dressing [13].
In Russia, the ready-to-use multi-purpose aseptic
dressings with soaked coating and long period of moisture keeping, including
dressings for protection of prolapsed abdominal organs, are absent in equipment
of medical service of military forces of RF and in civilian healthcare. Within
the limits of the government defense order and the federal contract of special
medical technique, technologies and pharmaceuticals of Moscow Physico-Technical
Institute (State University) became the head executor of the research and
development work (RDW). The department of military field surgery of Kirov
Military Medical Academy made the military and scientific follow-up. As result
of RDW, the experimental sample of aseptic dressing for protection and moisture
of prolapsed organs was made (the item index – AP-A). This sample was offered
to include into the equipping of medical services of Russian military forces.
It will influence on the rate of peritonitis and other severe complications at
the hospital stage.
Objective of the study was the development of the adequate
experimental model of the open abdominal injury, accompanied by internal organs
eventration, and assessment of the effectiveness of the developed aseptic
abdominal dressing to protect and hydrate eventrated organs in the prevention
of abdominal cavity infectious complications.
MATERIALS AND METHODS
The preliminary results gave the safest and most
appropriate (according to requirements for protection and moisture of prolapsed
internal abdominal organs) composition of aseptic dressing. Then the patent for
the invention No.184147 was received: aseptic dressing for protection and
moisture of prolapsed abdominal organs [14]. The composition of the aseptic
abdominal dressing (AAD): spunbond nonwoven fabric (100 % polypropylene) soaked
with vinylin-silicone gel (8 ± 1 g); vynylin – mass proportion – 85 + 1 %;
silicone fluid PMS-10 – mass proportion 15 + 1 %.
With consideration of the single publication in the
available literature relating to modeled eventration in laboratory animals
(rats) in the experimental study of regeneration processes in small intestine
[15], the original model of eventration in laboratory animals (male rats) was
developed [16]. For final tests of AP-A efficiency (Fig. 1), the model was
adapted to big laboratory animals (pigs), which corresponded to anatomical and
physiological properties of such examinations.
Figure 1. Aseptic dressing to protect and hydrate
eventrated (prolapsed) organs in sterile pouch. General view
The experiments with 7 male and female pigs of
Svetlogorsaya breed (body mass of 29-35 kg) were conducted on the basis of Almazov
National Medical Research Centre (St. Petersburg) in compliance with the Rules
for Research with Experimental Animals (the application for the Order of USSR
Health Ministry, 12 August 1977, No.755). The study protocol was approved by
the ethical committee of Kirov Military Medical Academy (St. Petersburg,
No.217, 25 December 2018).
The experiments were conducted in the vivarium. The
animals were kept at the environmental temperature from +19 to +23 °С in the
ventilated space without draught. The animals did not receive any food 24 hours
before surgery. The access to water was free. The experiment was completed with
euthanasia by means of narcosis overdose – introduction of 5 mg/kg of Zoletil
100 (Vibrac, France) with lethal dosage (3 narcosis doses). The bodies were cremated.
The
efficiency of AP-A was estimated with laboratory (blood clinical analysis,
microbiological study), instrumental, morphological techniques, expertise
estimation of specialists).
The blood clinical analysis was conducted with the
veterinary hematological analyzer Abacus Junior 30 (Diatron, Austria).
The microbiological study of peritoneal effusion was
conducted for estimation of AP-A for prevention of wound infection in the
experimental model of eventration. The materials were selected in compliance
with the guidelines (MU 4.2.2039-05) in the day of primary surgery and in the
day of relaparotomy. The samples were delivered to the laboratory within two
hours. Primary isolation and bacteriological studies were conducted in
compliance with regulatory documents [17, 18]. Chromogenic agar was additionally
used in primary isolation [19]. The isolation was conducted with the
semiquantitative method. The classic bacteriological methods were used for
separation and identification of aerobic and facultative anaerobic bacteria.
Totally, 14 biological samples were studied.
Intrasurgical laser doppler flowmetry (ISLDF) with the
laser analyzer of capillary perfusion LAKK-M (OOO NPP LASMA, Moscow) was used
for estimation of small intestine microcirculation. The main parameters of
microcirculation were registered:
- mean arithmetic value of microcirculation (Mcc)
describing the mean value of perfusion of volume unit of tissue per time unit
(perfusion units, p.u.);
- mean-square deviation of blood flow variations (σ) – blood flow modulation (mainly, by means of active
(endothelial, miogenic and neurogenic mechanism of vascular lumena regulation),
and passive (extrasystemic microcirculation of pulse wave from arteries and
pulse wave in venules) factors), or flax (measured in p.u.);
-
variation coefficient (Kv) characterizing the ratio between variability in
perfusion (flax) and mean perfusion (M) in a studied region, indicating the
percentage participation of active factors of regulation in total modulation of
tissue perfusion (measured with %), and oscillatory process determined by
endothelial (AE), neurogenic (AN), myogenic (AM), respiratory (R), cardiac (C)
factors of microcirculation control.
The
received parameters were analyzed with WPT. The components of microvascular
tone were calculated: myogenic (tone of metarterioles and precapillary
sphincters, M): MT = (σ × AP) / (AM × Mcc); neurogenic (tone of precapillary resistive microvessels,
N): NT = (σ
× AP) / (AN × Mcc); shunting index (the ratio between shunting and
nutritive blood flow, SI): SI = AN / AM, σ – flax, AP – mean arterial pressure; Mcc – mean
arithmetic value of microcirculation, AN and AM – maximal average amplitudes of
oscillations of sympathetic adrenergetic and myogenic ranges of frequencies.
After completion of the study, the normal values were calculated for analysis
of influence of each link on blood flow modulation (((А/3σ) × 100 %) and mean perfusion (A/M) × 100 %)) [20].
The materials for morphological study were
microsamples produced from parts of prolapsed loops of small intestine of pigs
ethtanized during the experiment.
The light-optical estimation included the fragments
with the most intense macroscopic changes in each group. 10 randomly selected vision
fields were used for estimation of focal reactive changes in intestinal wall in
condition of one-layer epithelium covering the serosa of small intestine. The
materials were estimated with histological slices (5 mcm) with rotation
microtome Leica RM2125 RTS (Leica Instruments GmBH, Germany) and stained with
hematoxiline and eosine according to the common technique, with microscope
Zeiss Axio Imager Z2 (Carl Zeiss Microscopy GmbH, Germany) and Zen 2 (blue) software
in compliance with the regulatory documents [21].
The expert evaluation method was realized by two
surgeons in two stages: 3 hours after application of dressing, on the days 3-5
during relaparotomy. The following criteria were used: dressing adhesion,
presence of adhesion process in abdominal cavity, fibrination, peritonitis,
values of blood clinical analysis and microcirculation, findings of
microbiological and morphological studies.
In the surgery day, the premedication was performed
with intramuscular introduction of Zoletil 100 (5 mg/kg). Animals were fixed on
the surgical table in supine position with spread extremities. Tracheal intubation
was conducted. During the whole experiment, intermittent positive pressure
ventilation (IPPV) was conducted with frequency of 12-15 inspirations per
minute, with inhalation of 100 % oxygene. Anaesthetic induction included 5 % of
total value for anesthesia supporting – 2-4 % of total sevoflurane (Baxter
Healthcare Corporation, USA).
For arterial pressure monitoring (AP) in the right inguinal
region, the introducer 5Fr was placed into the right femoral artery by means of
puncture with ultrasonic control (SonoScape Company Limited, China). 4Fr
introducer was placed into the left femoral artery for sampling the venous
blood for clinical analysis. Then the labeling of wound region (10 cm) was made
on the abdominal surface (Fig. 2).
Figure 2. The incision size, dorsal position of the animal
For exclusion of background abnormalities, the X-ray study of the animals’ chest was conducted (Philips Medical Systems Niederland B.V., Netherlands). The basic and following hemodynamic values (saturation, RR, HR, AP, respiratory volume (RV)) was realized according to monitor values (Shenzhen Mindray Bio-medical Electronics Co., Ltd., China). The eventration was modeled in the pararectal region to the left by means of minilaparotomy. The materials were collected from the abdominal cavity by conduction of microbiological study. With use of the pincers, the intestine loops were retrieved onto the anterior abdominal wall (Fig. 3). The visual examination of the small intestine and measurement of basic level of microcirculation with ISLDF and LAKK-M analyzer is shown in the figures 4 and 5.
Figure 3. Eventration
modelling
Figure
4. Preparation for intraoperative laser doppler
flowmetry (IOLDF) on the small intestine using capillary circulation laser
analyzer (CCLA)
Figure 5. The computer assisted CCLA
The efficiency of AP-A was estimated on the following
stages in combination with abdominal compression bandage dressing for 3 hours.
The prolapsed loops of small intestine were covered with AP-A in
envelope-shaped form. A doughnut-shaped gauze roll (prepared preliminary) was
placed over the aseptic dressing and around prolapsed organs (Fig. 6). The roll
was used for amortization and prevention of compression of prolapsed loops.
Figure
6. Covering of small intestine loops with AP-A and adjustment
of gauze and cotton dressing around loops
For external bleeding arrest from the abdominal wall wound and for prevention of entraptment of prolapsed intestinal loops, KBP-A was placed onto animals’ bodies around the abdomen. A degree of external compression of KBP-A was estimated and controlled with tension sensors, which were placed under the inferior part of KBP-A after application (Fig. 7). The compression degree did not exceed 2 mm Hg (minimal degree of compression). Then the animals were observed within 3 hours. The hemodynamic parameters were controlled.
Figure
7. Application of the compression abdominal bandage
(CAB) and evaluation of external compression force with digital facility
KBP-A was removed at the next stage. The gauze roll
and AP-A were removed. A degree of adhesion to prolapsed loops was estimated
visually according to the criteria. LAKK-M was used for visual estimation of
the intestine and the basic level of microcirculation. Then the prolapsed loops
of small intestine were placed into the abdominal cavity, and the laparotomy
wound was sutured. The aseptic dressing was placed onto the abdominal wall
dressing, and the animals were placed into the individual cells and were
followed-up during 3-5 days.
3 (n = 3), 4 (n = 3) or 5 (n = 1) days later, the
blood was sampled from each animals for hematological examination. Relaparotomy
and abdominal cavity sampling were performed for microbiological study. The
condition of loops of prolapsed intestine and the intensity of the adhesion
process were estimated in compliance with developed criteria (adhesion of a
drape, peritonitis, adhesion and other complications).
LAKK-M with ISLDF was used for estimation of influence
of AP-A on small intestine microcirculation. Before initiation of the
experiment, the device was calibrated. After eventration modeling, the analyzer
probe was placed in perpendicular manner to the small intestine wall from the antimesenteric
edge of the small intestine. The microcirculation parameters were registered three
times at the following stages of the experiment: before application of dressing
and after relaparotomy on the days 3, 4 or 5. The registration lasted for 8
minutes – time required for registration of some slow and high-frequency
variations of blood flow. On the final stage, the general estimation of
efficiency of AP-A was conducted which included the results of primary blood
analysis, 3 hours after AP-A, 3-5 days before relaparotomy. After the
experiment completion, the mobilization and resection of the prolapsed part of
the intestine were carried out for the morphological examination.
The quantitative data was presented as mean values (M ± m). The data was
kept in the experiment protocols. The critical level of significance for
statistical hypotheses was 0.05. Non-parametrical statistical methods were used
for the statistical analysis. Microsoft Excel 2010 (Microsoft, USA) was used
for collection and preparation of the data.
The study was conducted as a part of the service
contract No. EP 18-181, 1 June 2018, between Moscow Physico-Technical Institute
(National Research University) and Almazov National Medical Research Centre
during realization of the federal military order and the state contract.
RESULTS AND DISCUSSION
The study of abdominal organ eventration included seven animals (the mean body mass of 32.4 kg [28.5-35.0]). The values of clinical analysis of the blood did not change significantly during the experiment and corresponded to the reference values for this type of animals (the table 1).
Table 1. The analysis of general blood test findings in the experiment, M ± m
|
Values |
Leukocytes, ×109/l |
Red blood cells, ×1012/l |
Hemoglobin, g/l |
Platelets, ×109/l |
|
Before experiment |
19.6 ± 1.2 |
6.1 ± 0.2 |
107.2 ± 3.2 |
488.7 ± 37.4 |
|
hours after application of AP-A |
20.6 ± 2.4 |
6.3 ± 0.2 |
112.4 ± 5.2 |
487.8 ± 37.3 |
|
3, 4 and 5 days after removal of AP-A |
26.3 ± 3.8 |
6.2 ± 0.2 |
109.7 ± 3.2 |
472.8 ± 41.3 |
|
Reference values |
16.5 ± 1.1 (11.0-22.0) |
7.2 ± 0.5 (5.0-9.5) |
132.0 ± 6.6 (99-165) |
450.0 ± 50.0 (200-700) |
The microbiological study of the basic samples showed
no bacterial growth in three animals both in primary and recurrent study. The
inoculation of materials, which were sampled in the surgery day, identified the
gram-negative bacteria: Pseudomonas sp., Stenotrophomonas maltophilia and Escherichia coli (104–108 CFU/ml). The first two microorganisms – members of the group
of free-living non-fermenting (aerobic) bacteria, common in outside environment
– could seed the water or various objects of the vivarium. E. coli could
possibly get onto the animal’s skin from the contaminated footcloth. In two
animals, the gram-negative bacteria were separated from the samples, which were
taken during relaparotomy: one with Proteus
mirabilis, another – association of two intestinal bacteria (Escherichia coli and Proteus mirabilis) at the level of 105–106
CFU/ml. Possibly, these bacteria appeared on the skin from the
contaminated floor, and they contaminated the samples during collection. The
possibility of contamination is also indicated by the absence of clinically
evident signs of infection and inflammation process on the skin in the
abdominal cavity during relaparatomy.
The histological study of the samples of the small
intestine was conducted on the basis of the fact that the sample, which is
taken without surgical interventions, is considered as control (n = 1). After
the study of tissue structure of the control sample and considering as relative
norm (Fig. 8), other samples were estimated in comparison with it. All samples,
except for control one, showed some insignificant reactive changes in cells of tessellated
epithelium covering the serosa of the small intestine, namely, mild basophily
of mesotheliocyte nuclea at the background of preserved cytoarchitectonics of mesothelium
layer (Fig. 9).
Figure
8. Pig’s small intestine microslides (normal). Magnification 400x
Figure 9. Pig’s small intestine microslide, the 3rd day following AP-A. Magnification
400x The control group 1.
Along with preservation of cytoarchitectonics, one
should note that the studied samples showed some changes in vascular bed
elements and in the submucosal basis in all experimental groups: enlargement of
endotheliocytes, vascular congestion with single perivascular cellular response
with appearance of leukocytes behind the limits of the vascular bed (leukocytic
response).
Some mild morphological changes in tissue elements
were identified as result of the morphological study of the samples from the
experimental (testing) group of animals (n = 7) in comparison with the control
one (n = 1). These facts testify the absence of critical influence of ischemia
on tissues during use of AP-A within 3 hours.
The time course of mean results of the
microcirculation of prolapsed intestinal wall during the experiment is shown in
the figure 10.
Figure 10. The analysis of microcirculation (MC) findings,
mean root square deviation in blood flow (σ) and perfusion coefficient of variation (Kv) at different stages of the
experiment.
The basic values of the microcirculation parameters
were: Mcc – 18.4 [17.1; 19.0] p.u, σ – 1.1 [1.0; 1.7] p.u., Kv – 5.8 [5.0; 11.4] %. During
the experiment, the level of perfusion (Mcc) did not change significantly and
was at the level of the basic (background) values (p > 0.05). So, at the
moment of completion of the experiment (after days 3-5), this value was 22.6
[8.0; 22.8] p.u.
Three hours after application of AP-A, we observed a
statistically significant trend to the increase in the coefficient of perfusion
variation (Kv) by means of increasing variability of blood flow (σ) in almost non-alternating value of microcirculation
(Mcc) that can be determined by intensification of active and passive
mechanisms of blood flow control (the table 2).
Table 2. Microblood flow in the experiment (enhancement of passive mechanisms of tissue perfusion control)
|
Value |
0 hours |
3 hours |
72-120 hours |
|
|
E |
А |
0.19 [0.13; 0.20] |
0.05 [0.04; 0.23] |
0.19 [0.07; 0.30] |
|
(А/3σ) × 100 % |
4.80 [3.54; 5.54] |
1.53 [1.20; 4.21] |
3.91 [3.53; 5.52] |
|
|
(А/М) × 100 % |
1.54 [1.03; 2.05] |
2.33 [0.43; 2.41] |
1.03 [0.71; 1.61] |
|
|
N |
А |
0.25 [0.09; 0.26] |
0.10 [0.03; 0.22] |
0.18 [0.17; 0.51] |
|
(А/3σ) × 100 % |
4.95 [3.23; 5.88] |
3.84 [0.93; 4.58] |
4.17 [3.53; 5.52] |
|
|
(А/М) × 100 % |
1.58 [0.88; 1.80] |
2.12 [0.57; 2.46] |
1.26 [0.83; 4.38] |
|
|
M |
А |
0.69 [0.19; 0.76] |
0.24 [0.08; 0.37] |
0.72 [0.51; 0.66] |
|
(А/3σ) × 100 % |
6.94 [5.73; 11.25] |
6.95 [2.70; 10.68] |
7.96 [6.58; 15.91] |
|
|
(А/М) × 100 % |
2.57 [0.99; 5.24] |
1.86 [1.63; 1.99] |
3.19 [2.57;4.13] |
|
|
R |
А |
0.40 [0.23; 0.55] |
0.41 [0.16; 0.45] |
0.53 [0.45; 0.66] |
|
(А/3σ) × 100 % |
6.29 [5.17; 10.98] |
14.90 [4.58; 15.65] |
7.52 [5.13; 16.83] |
|
|
(А/М) × 100 % |
1.53 [1.19; 3.97] |
2.38 [1.91; 2.46] |
4.00 [3.78; 4.96] |
|
|
C |
А |
0.73 [0.49; 0.83] |
0.32 [0.18; 0.69 |
0.67 [0.59; 0.90] |
|
(А/3σ) × 100 % |
13.45 [7.84; 16.10] |
11.36 [5.13; 14.43] |
12.68 [7.06; 19.66] |
|
|
(А/М) × 100 % |
4.28 [2.46; 4.94] |
2.79 [2.24; 3.52] |
4.00 [3.78; 4.96] |
|
|
SV |
0.48 [0.38; 1.11] |
0.92 [0.43; 1.11] |
0.52 [0.29; 0.86] |
|
Note: E, N, M, R, S – endothelial, neurogenic, myogenic, respiratory, cardiac links of regulation of microblood flow correspondingly; A – maximal amplitude of each link of regulation of microcirculation; (А/3σ) × 100 % – normalized amplitude, (А/М) × 100 % – reduced amplitude, SV – shunting value.
However the statistically unreliable trend to
decreasing maximal amplitudes and to influence on blood flow modulation of
endothelial, neurogenic and myogenic rythmes allows supposing the activation of
passive mechanisms of tissue perfusion regulation (indirectly shown by a trend
to increasing influence of respiratory rate on microcirculation modulation).
The prevalence of the respiratory component (venous stasis) is possibly
determined by experimental conditions – long term anesthesia and adynamia.
Postsurgical eventration of internal organs is often
accompanied by development of pathological processes in the abdominal cavity
[16]. The most common ones are intestinal wall edema and disorder of intestinal
microcirculation, deserosing of a part of the intestine with subsequent
perforation and necrosis of the intestinal wall, formation of adhesive
obstruction and interintestinal abscesses and, certainly, development of
peritonitis. During estimation of results of AP-A, we considered the possible
signs of the mentioned processes (the table 3).
Table 3. Evaluation of the effectiveness of AP-A used to cover small intestine loops in the case of eventration
|
Criterion, points |
Animal’s number, points |
||||||
|
1 |
2 |
3 |
4 |
5 |
6 |
7 |
|
|
1) dresing adhesion to eventrated loop of small intestine 3 hours after application of AP-A: |
1 |
1 |
2 |
1 |
1 |
0 |
1 |
|
2) hyperemia and edema of loops: |
0 |
1 |
0 |
1 |
0 |
1 |
0 |
|
3) condition of intestine wall: |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
4) adhesion process: |
0 |
1 |
1 |
0 |
1 |
0 |
0 |
The estimation of the experimental sample of AP-A
after 3 hours of influence on prolapsed loops of the small intestine showed
that the dressing could preserve the safe adhesive properties in 6 of 7 cases,
with one case with intestinal wall erosions. After the days 3-5, during
relarapotomy, the edema and hyperemia of the intestine were observed in 3 of 7
cases, the adhesion process and fibrin deposits – in one case. Some single
loose adhesions between the small intestine loops were noted in 3 cases. There
were not any signs of peritonitis in 7 animals.
According to results of the experimental study, one
can suppose that the use of AP-A in the opened abdominal injury with
eventration of internal organs (small intestine loops) decreases the risk and
incidence of peritonitis and do not make any negative influence on intestinal
wall.
CONCLUSION
1. The current standard improvised methods for
protection and moisture of prolapsed abdominal organs (gauze wads with 0.9 %
saline or Vaseline) in condition of staged treatment and emergency medical care
require for revision.
2. According to received experimental data, the
testing samples of aseptic dressing (AP-A) preserved the required moisture and
protected the prolapsed abdominal organs, demonstrated the safe adhesive
properties and prevented the development of local and general complications in
early postsurgical period.
3. Abdominal aseptic dressing (the item index - AP-A)
can be used for protection and moisture of prolapsed abdominal organs at the
prehospital stage in conditions of emergency medical care and in the system of
staged treatment.
Information on conflict of interests
The study was conducted without sponsorship. The authors declare the absence of any clear and potential conflicts of interests relating to publication of this article.
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